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Biomedical subjects

H W Lim

Publications and source records attributed to H W Lim.

At least 19 recordsLinked to original sources
PubMed1992

Photosensitivity, abnormal porphyrin profile, and sideroblastic anemia.

Cutaneous photosensitivity in a 43-year-old man with idiopathic sideroblastic anemia associated with an abnormal porphyrin profile is reported. This condition was associated with elevated free erythrocyte porphyrin, plasma protoporphyrin, urine porphyrins (predominantly coproporphyrin), stool porphyrins (predominantly protoporphyrin), decreased ferrochelatase activity, and deletion of portions of the long arms of chromosomes 18 and 20. Five other patients with sideroblastic anemia and abnormal porphyrin profiles have been described; all but one of these patients had photosensitivity. The porphyrin profile of this patient is similar to that of three other previously described patients.

Adult↗
PubMed1991

C5a, cutaneous mast cells, and inflammation: in vitro and in vivo studies in a murine model.

To evaluate further the interactions of C5a and mast cells in cutaneous inflammation, the ability of human native C5a (nC5a) (10 to 500 ng/ml) and human recombinant C5a (rC5a) (10 ng/ml to 100 ng/ml) to induce histamine release from purified BALB/c cutaneous mast cells (CMC) and peritoneal mast cells (PMC) was analyzed. It was found that nC5a induced histamine release from CMC but not from PMC, with a maximal net release at 250 ng/ml nC5a (22.8 +/- 2.6%). Kinetic experiments demonstrated that nC5a-induced maximal net histamine release occurred 5 min after the presentation of this stimulus (25.8 +/- 6.0%). Using rC5a and CMC, dose-response studies indicated a maximal net release of 7.0 +/- 1.7% at rC5a of 10 ng/ml, and kinetic studies showed a maximal net release at 5 min of incubation (12.9 +/- 1.6%). Release induced by rC5a was calcium-dependent, and peaked at 30 degrees C. These results indicate that functional heterogeneity exists between the CMC and the PMC of BALB/c mice, that C5a is a relevant stimulus for characterization of this heterogeneity, and that CMC from these animals can serve as a convenient in vitro model for the study of human C5a-mast cell interactions. In vivo, injections of nC5a (25-100 ng) and rC5a (25-100 ng) into the skin of BALB/c mice induced an increase in cutaneous vasopermeability, as assessed by the extravasation of intravenously injected 125I-bovine serum albumin. nC5a induced a dose-dependent increase in vasopermeability, whereas alterations induced by rC5a plateaued at 50 ng. The C5a-induced vasopermeability was markedly enhanced in animals that had been previously treated with an inhibitor of serum carboxypeptidase, which converts C5a to the less potent derivative, C5a des Arg. These findings suggest that carboxypeptidase plays an important role in vivo in the modulation of C5a-induced cutaneous inflammation in murine skin.

Animals↗
PubMed1991

Irradiation of protoporphyric mice induces down-regulation of epidermal eicosanoid metabolism.

This study investigated the effect of radiation on clinical and histologic changes, and on cutaneous eicosanoid metabolism, in Skh:HR-1 hairless albino mice rendered protoporphyric by the administration of collidine. At 0.1-18 h after exposure to 12 kJ/m2 of 396-406 nm irradiation, thicknesses of back skin and ears were measured, and histologic changes were evaluated by using hematoxylin and eosin (H-E) and Giemsa's stains. Activities of eicosanoid-metabolizing enzymes in epidermal and dermal homogenates were assessed by incubating the tissue homogenates with 3H-AA, followed by quantitation of the eicosanoids generated by radio-TLC. In irradiated protoporphyric mice, an increase of back-skin thickness was noted at 0.1 h, reaching a peak at 18 h, whereas maximal increase in ear thickness was observed at 12 h. Histologic changes included dermal edema, increased mast cell degranulation, and mononuclear cells in the dermis. In these irradiated protoporphyric animals, generations of 6 keto-PGF1a, PGF2a, PGE2, PGD2, and HETE by epidermal eicosanoid-metabolizing enzymes were markedly suppressed at all the timepoints studied. Dermal eicosanoid-metabolizing enzymes of irradiated protoporphyric mice generated increased amounts of PGE2 and HETE at 18 h, probably reflecting the presence of dermal cellular infiltrates. The suppression of the activities of epidermal eicosanoid-metabolizing enzymes was prevented by intraperitoneal injection of WR-2721, a sulfhydryl group generator, prior to irradiation, suggesting that the suppression was secondary to photo-oxidative damage of the enzymes during the in vivo phototoxic response. These results suggest that the effect of protoporphyrin and radiation on cutaneous eicosanoid metabolism in this animal model in vivo is that of a down regulation of the activities of epidermal eicosanoid-metabolizing enzymes.

Amifostine↗
PubMed1991

Are topical corticosteroids useful adjunctive therapy for the treatment of psoriasis with ultraviolet radiation? A review of the literature.

Adjunctive topical corticosteroids are often administered with UV-B phototherapy or oral psoralen plus UV-A (PUVA) photochemotherapy for the treatment of psoriasis. Five studies comparing PUVA alone with PUVA and topical corticosteroid preparations showed more rapid rates of clearing and a smaller total UV-A exposure with the latter regimen. However, one study demonstrated a higher relapse rate in association with corticosteroid use. Further studies to better define these risks are recommended. Six of seven reports evaluating the use of topical corticosteroid preparations with UV-B phototherapy failed to demonstrate an advantage to this regimen when compared with UV-B phototherapy alone. Therefore, the use of a topical corticosteroid preparation with UV-B phototherapy for the treatment of psoriasis is not recommended.

Administration, Topical↗
PubMed1990

Chronic actinic dermatitis. Study of the spectrum of chronic photosensitivity in 12 patients.

Twelve patients with photodermatitis for longer than 3 months' duration were identified: 1 patient with chronic photocontact dermatitis, 1 with persistent photosensitivity following exposure to a systemic medication, 6 with persistent light reactivity, and 4 with actinic reticuloid. There were 10 men and 2 women, ranging in age from 27 to 81 years, with a mean age of 62 years. The duration of the eruption ranged from 6 months to 20 years. Persistence of photosensitivity to quinidine, which is analogous to persistent light reactivity, was documented in 1 patient, and evolution from photocontact dermatitis to actinic reticuloid was observed in 2 others. These data, along with those reported in the literature, indicate that chronic photocontact dermatitis, persistent photosensitivity to systemic agents, persistent light reactivity, photosensitive eczema, and actinic reticuloid should be considered as entities occurring along a continuum, and the term "chronic actinic dermatitis" is suggested to refer to these entities. Eight (67%) of the 12 patients had skin type VI and 2 others (17%) had skin type V, percentages markedly higher than those of the general patient population, demonstrating that chronic actinic dermatitis is not uncommon among individuals with dark skin.

Adult↗
PubMed1990

Mast-cell heterogeneity: functional comparison of purified mouse cutaneous and peritoneal mast cells.

To investigate the functional heterogeneity of mouse mast cells, we extracted and purified cutaneous and peritoneal mast cells from 10- to 18-week-old BALB/c mice and compared their responses to secretagogues. Cutaneous mast cells (CMC) were extracted from mouse ears after digestion with hyaluronidase and collagenase in MEM containing 25% fetal calf serum and purified on a discontinuous Percoll gradient. The histamine content of cells obtained from the 30/40% interface was 1.0 +/- 0.1 pg/cell (mean +/- SE), with a mast-cell purity of 68.6 +/- 4.4% and a viability of greater than 93%. Peritoneal mast cells (PMC) were obtained by lavage with modified Tyrode's buffer followed by purification on 22.5% and 3-9% metrizamide gradients. The histamine content of cells was 12.2 +/- 0.8 pg/cell, with a mast-cell purity of 95.9 +/- 0.6% and a viability of greater than 95%. Histamine release induced by A23187 from CMC peaked at 3.0 microM A23187 (19.1 +/- 4.2%), at 3.0 min (22.3 +/- 2.3%), and at 30 degrees C (17.6 +/- 2.6%). In contrast, histamine release from PMC peaked at 8.0 microM of A23187 (49.4 +/- 12.1%) and at 15.0 min (48.5 +/- 12.2%). Release of histamine from PMC was observed at all the temperatures tested from 22 to 45 degrees C. Histamine release from CMC and PMC induced by A23187 was calcium dependent. Histamine release induced by compound 48/80 from CMC peaked at 0.5 micrograms/ml of compound 48/80 (23.0 +/- 7.4%) and at 5.0 min incubation (16.3 +/- 2.0%), whereas release from PMC peaked at 10.0 micrograms/ml (31.9 +/- 2.6%); release from PMC was similar at all the time points examined (1-15 min). Histamine release induced by substance P (SP) from both CMC and PMC peaked at 5.0 microM (18.8 +/- 6.6% and 12.6 +/- 3.7%, respectively); however, the maximal release from CMC occurred at 3.0 min (18.2 +/- 3.2%) and from PMC at 30.0 min (11.4 +/- 2.0%). SP-induced histamine release from CMC was calcium dependent, whereas release from PMC was only partially inhibited by EDTA. This study demonstrated that functional heterogeneity exists between these two populations of mast cells.

Animals↗
PubMed1990

The complement system. Activation, modulation, and clinical relevance.

Activation of the classic or the alternative pathway of the complement system results in the generation of biologically active products and the assembly of MAC. Homeostasis is achieved by the presence of control proteins that modulate the activation at various levels. Complement proteins play an important role in the pathogenesis of several dermatologic disorders. Their deficiency is associated with impairment of host-defense; uncontrolled activation of the system results in the development of angioedema or chronic hemolysis.

Complement Activation↗
PubMed1989

Cutaneous inflammation: effects of hydroxy acids and eicosanoid pathway inhibitors on vascular permeability.

Four metabolic products of arachidonic acid lipoxygenation, 5-hydroxyeicosatetraenoate (5-HETE), 12-HETE, 15-HETE, 5(S),12(S)-DiHETE, were injected intradermally into depilated dorsae of albino guinea pigs. The presence of intravenously injected 125I-bovine serum albumin (10uCi/kg) in 13-mm punch biopsy specimens served as a marker for altered vascular response; histologic changes were evaluated at 6 and 24 h after the injection in 1-micron-thick sections. Thirty minutes after the injections of 15 nanomoles and 60 nanomoles of 5-HETE, the ratios of radioactivity in HETE-injected to that in buffer-injected sites were 1.35 +/- 0.06 (mean +/- SE) and 2.80 +/- 0.27, respectively. Corresponding effects of 15-HETE were 1.39 +/- 0.17 and 1.63 +/- 0.21, respectively. Values for 60 nanomoles of 12-HETE and 5,12-DiHETE were intermediate in comparison with the above eicosanoids. The most notable histologic changes were a neutrophilic infiltrate induced by 12-HETE at 6 and 24 h, and neutrophilic and eosinophilic infiltrates in response to 5,12-DiHETE injection at 6 and 24 h. Effects of topically applied eicosanoid pathway inhibitors were also evaluated, using intradermally injected sodium arachidonate (AA) as agonist. Three mixed cyclooxygenase/lipoxygenase inhibitors, BW755C, phenidone, and nordihydroguaiaretic acid, suppressed vascular response by 9%, 9%, and 6% for 150 nmol of AA, and by 9%, 13%, and 12% for 300 nmol of AA, respectively. The cyclooxygenase inhibitor, indomethacin, induced suppressions of 39% for 150 nmol AA and 22% for 300 nmol AA, respectively. These data demonstrate that metabolites of both cyclooxygenase and lipoxygenase eicosanoid pathways are involved in alteration in vascular response accompanying cutaneous inflammation.

Animals↗
PubMed1989

The late phase of hematoporphyrin derivative-induced phototoxicity in mice: release of histamine and histologic changes.

This study was designed to directly examine the role of mast cells and the histologic changes in the late phase (4-48 h) of hematoporphyrin derivative-induced phototoxicity. BALB/c mice were rendered phototoxic by intraperitoneal injection of HpD, followed by exposure to 1.59 kJ/m2 of 396-406 nm radiation. Immediately before radiation, and at 4, 8, 12, 18, 24 and 48 h after radiation, the ear thickness, serum histamine levels and histologic changes of ears were examined. A maximal net increase in ear thickness of 33.5 +/- 0.3 X 10(-2) mm (mean +/- SE) was noted at 12 h, associated with a maximal net increase of serum histamine (43.3 +/- 11.6 ng/ml, mean +/- SE), and a maximal mast cell degranulation. Other histologic changes consisted of mild epidermal spongiosis at 18-24 h, and a predominant neutrophilic infiltrate, which peaked at 24 h (211.6 +/- 0.4 cells/mm2). No significant alteration was observed in control mice. These data indicated that mast cells participate in the late phase of HpD-induced phototoxicity in mice.

Animals↗
PubMed1989

Effects of chloroquine on release of mediators from mast cells.

This study was designed to investigate the effect of chloroquine (CQ) on the release of preformed and generated mediators from rat serosal mast cells (greater than 90% pure). CQ alone (10-1,000 micrograms/ml) induced the release of preformed mediators, while stimulation with calcium ionophore A23187 of CQ-treated cells resulted in suppressed releases of both preformed and generated (particularly prostaglandin D2) mediators. These effects were calcium-independent and reversible. Whether these results partly explain the efficacy of CQ in the treatment of mast cell-mediated dermatoses remains to be further investigated.

Animals↗
PubMed1989

Mechanisms of phototoxicity in porphyria cutanea tarda and erythropoietic protoporphyria.

The porphyrias are the only group of diseases caused by endogenous phototoxic agents. While patients with erythropoietic protoporphyria and those with porphyria cutanea tarda both have skin lesions on sun-exposed areas, there are differences in their cutaneous manifestations. Based on information discussed in this chapter, the following pathophysiologic mechanisms can be proposed. In porphyria cutanea tarda, photoactivation of the complement system in the presence of uroporphyrin results in activation of dermal mast cells, which release their proteases. This results in dermal-epidermal separation, reflected clinically as skin fragility and vesicles. The interaction between activated mast cells with fibroblasts, the nature of which is still unclear, may contribute to fibrosis and sclerodermoid skin changes. The stimulatory effect of uroporphyrin on collagen biosynthesis by fibroblasts, which occurs independent of irradiation, may be responsible for the sclerodermoid lesions seen at sun-exposed as well as sun-protected areas. In erythropoietic protoporphyria, mast cell activation can occur as the result of complement activation induced by protoporphyrin and irradiation. Protoporphyrin and irradiation may also directly induce the release of preformed and generated mediators from mast cells, a process mediated at least in part by peroxidation. The release of mast cell mediators may account for the erythema, edema, and urticaria observed in patients with erythropoietic protoporphyria upon exposure to sunlight. Interaction of mast cells with fibroblasts, and the direct membrane-damaging effect of protoporphyrin and irradiation on the latter, may contribute to the waxy thickening of skin seen in chronically sun-exposed areas of these patients. There are, however, many unanswered questions. What accounts for the different biological effects of mast cell-derived mediators: dermal-epidermal separation in one, erythema and urticaria in the other? The fragmentation of dermal collagen bundles associated with cleavage beneath the lamina densa, and the hyperpigmentation and hypertrichosis observed in some patients with porphyria cutanea tarda remain unexplained. What is the mechanism of the reduplication of blood vessel basal lamina in the non-sun-exposed areas of both types of patient? Are there any roles for cytokines and epidermal cell-derived eicosanoids? While it is clear that the pathogenesis of cutaneous lesions in porphyria cutanea tarda and erythropoietic protoporphyria involves interactions among inflammatory mediators and various cells in skin, much still needs to be done to further our understanding of their pathophysiology.

Animals↗
PubMed1989

Effects of porphyrins on skin.

Porphyrins and radiation induce activation of the complement system, release of mediators from mast cells, dermal accumulation of neutrophils, and activation of factor XII-dependent pathways. Recent studies have also shown that porphyrins and radiation have profound effects on the eicosanoid metabolism of mast cells, endothelial cells, macrophages and epidermal and dermal homogenates. In vitro, prostaglandin D2 (PGD2) was generated when mast cells were exposed to protoporphyrin and radiation. Exposure of cultured human umbilical vein endothelial cells or human omental microvascular endothelial cells to uroporphyrin or protoporphyrin and radiation resulted in predominant generation of PGF2 alpha, while PGE was generated after the exposure of macrophages to Photofrin II and radiation. Activities of epidermal eicosanoid-metabolizing enzymes in protoporphyric mice were suppressed following in vivo exposure to radiation, whereas activities of the dermal enzymes were enhanced 18 h after radiation. These effects of porphyrins on skin contribute to the development of porphyrin-induced cutaneous phototoxicity, which is seen in patients with porphyrias and as a consequence of photodynamic therapy.

Animals↗
PubMed1988

Effect of ultraviolet radiation and PUVA on mediator release from purified mast cells.

Exposure of highly purified rat serosal mast cells to UVA (34-340 kJ/m2), in the presence or absence of 8-methoxypsoralen (100 ng/ml), or to UVB (160-640 J/m2), resulted in dose-dependent releases of mast cell preformed mediators, as measured by the release of radioactivity from 3H-serotonin-labeled cells. The net release ranged from 2.3% to 14.2%. The above treatments had no effect on mediator release induced by subsequent incubation with calcium ionophore A23187 (0.4 and 4.0 mumol/l) or with compound 48/80 (1.0 microgram/ml), with the exception that exposure to UVB did suppress the release induced by the latter. These results indicate that under clinically relevant conditions, the direct effect of in vitro ultraviolet radiation on mast cells did not alter the ability of these cells to respond to subsequent stimulation with secretagogues.

Animals↗
PubMed1987

Photodermatoses.

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Bibliographies as Topic↗